Cardiovascular disease (CVD) has become one of the commonest causes of comorbidity and mortality among People living with human immunodeficiency virus (HIV) (PLWH) on antiretroviral therapy (ART). Nearly 50% of PLWH are likely to have an increased risk of developing CVD, including coronary heart disease, cerebrovascular disease, peripheral artery disease and aortic atherosclerosis. Aside from the common risk factors, HIV infection itself and side effects of antiretroviral therapy contribute to the pathophysiology of this entity. Potential non-pharmacological therapies are currently being tested worldwide for this purpose, including eating patterns such as Intermittent fasting (IF). IF is a widespread practice gaining high level of interest in the scientific community due to its potential benefits such as improvement in serum lipids and lipoproteins, blood pressure (BP), platelet-derived growth factor AB, systemic inflammation, and carotid artery intima-media thickness among others cardiovascular benefits. This review will focus on exploring the potential role of intermittent fasting as a non-pharmacological and cost-effective strategy in decreasing the burden of cardiovascular diseases among HIV patients on ART due to its intrinsic properties improving the main cardiovascular risk factors and modulating inflammatory pathways related to endothelial dysfunction, lipid peroxidation and aging. Intermittent fasting regimens need to be tested in clinical trials as an important, cost-effective, and revolutionary coadjutant of ART in the fight against the increased prevalence of cardiovascular disease in PLWH. / Revisión por pares

Indiana University-Purdue University Indianapolis (IUPUI) / More than 20 million people have died of AIDS since the early eighties, while nearly 34 millions are currently infected with the HIV. Anti-retroviral therapy (ART) directed at key viral enzymes has changed AIDS from uniformly fatal to a manageable chronic disease. However, ART-associated drug resistance and toxicity have posed a great challenge for long-term management of the disease and have called for development of new therapeutics. In this study, we focused on the viral factor Nef and the host factor Sam68. Nef is a major pathogenic viral determinant for HIV-1, and no therapeutics have been targeted to this factor. Sam68 is indispensible for HIV-1 propagation. We revealed that Sam68 variants were very potent in preventing Nef expression. We found that these effects were associated with their ability to form a macromolecular structure called stress granules (SG). In addition, we demonstrated that these variants bound to nef mRNA in a sequence-specific manner. Furthermore, we showed that these variants co-localized with nef mRNA in SG. Importantly, we validated these findings in the context of HIV-1 infection of its natural target cells and found significant loss of Nef function in these cells. Taken together, these results demonstrate that SG induction and nef mRNA sequestration account for translational suppression of Nef expression and offer a new strategy for development of anti-HIV therapeutics. Sam68 is implicated in a variety of other important cellular processes. Our findings that Sam68 variants were able to induce SG formation prompted us to investigate whether wild-type Sam68 was also recruited to SG. We found that Sam68 was increasingly recruited into SG under oxidative stress, and that its specific domains were involved. However, Sam68 knockdown had no effects on SG assembly, suggesting that Sam68 is not a constitutive component of SG assembly. Lastly, we demonstrated that Sam68 complexed with TIA-1, an essential SG component. Taken together, these results provide direct evidence for the first time that Sam68 is recruited into SG through complexing with TIA-1, and suggest that SG recruitment of Sam68 and ensuing changes in Sam68 physiological functions are part of the host response to external stressful conditions.

Background: HIV is a condition that requires lifelong treatment. Treatment options currently consist of oral antiretroviral therapies (ART) taken once or twice daily. Long-acting injectable HIV treatments are currently in development to be administered monthly or every other month. Preferences for route of administration could influence treatment adherence, which could affect treatment outcomes. The purpose of this study was to examine patient perceptions of oral and injectable routes of administration for ART. Methods: Qualitative thematic analysis was conducted to examine 5122 online discussion threads by people living with HIV (PLHIV) in the POZ Community Forums from January 2013 to June 2018. Analysis focused on identifying perceptions of oral or injectable routes of administration for ART. Relevant threads were extracted and imported into the qualitative data analysis software package ATLAS.ti.8 so that text could be reviewed and coded. Results: Analyses identified 684 relevant discussion threads including 2626 coded quotations from online posts by 568 PLHIV. The oral route of administration was discussed more frequently than injectable (2516 quotations for oral; 110 injectable). Positive statements on the oral route of administration commonly mentioned the small number of pills (276 quotations), dose frequency (245), ease of scheduling (153), and ease of use (146). PLHIV also noted disadvantages of the oral route of administration including negative emotional impact (166), difficulty with medication access (106), scheduling (131), and treatment adherence (121). Among the smaller number of PLHIV discussing injectable ART, common positive comments focused on dose frequency (34), emotional benefits of not taking a daily pill (7), potential benefits for adherence (6), overall convenience (6), and benefits for traveling (6). Some comments from PLHIV perceived the frequency of injections negatively (10), and others had negative perceptions of needles (8) or appointments required to receive injections (7). Conclusions: Qualitative analysis revealed that route of administration was frequently discussed among PLHIV on this online forum. While many expressed positive views about their daily oral medication regimen, others perceived inconveniences and challenges. Among PLHIV who were aware of a possible monthly injectable treatment, many viewed this new route of administration as a convenient alternative with potential to improve adherence.

Introduction: Postpartum women living with HIV (WLWHIV) on antiretroviral therapy (ART) are at high risk of viraemia. We examined the association between unintended pregnancy and HIV viral load (VL) at 24 months postpartum in Cape Town, South Africa. Methods: Data are from a randomised trial that compared different ART delivery modalities for postpartum women aged at least 18 years who had initiated ART during their most recent pregnancy, had a VL<400 copies/ml in the previous three months, and had no comorbidities necessitating regular clinical follow-up. Pregnancy intentions regarding the most recent pregnancy were self-reported at enrolment into the study. VL was measured at 24 months postpartum, with elevated VL defined as VL≥1000 copies/ml. Chi-squared tests and logistic regression were used to examine predictors of unintended pregnancy. The impact of unintended pregnancy on elevated VL was examined using Poisson regression models. Results: Among 411 women included in the analysis (mean age: 28.7 years, 42% married/cohabiting, 75% with a parity≥2, and 86% with a VL<50 copies/ml), 57% reported that their most recent pregnancy was unintended. Compared to women aged 18-24 years, older women had a lower relative odds of unintended pregnancy [25-28 years, adjusted odds ratio (AOR): 0.34; 95% confidence interval (CI): 0.17-0.70; 29-34 years, AOR: 0.18; CI: 0.08-0.37; and ≥35 years, AOR: 0.35; CI: 0.14-0.89]. Additionally, unintended pregnancy was associated with being unmarried/not cohabiting (AOR: 4.44; CI: 2.78-7.09) and with higher parity (compared to parity=1: parity=2, AOR: 3.47; 95% CI: 1.86-6.50; and parity≥3, AOR: 6.38; 95% CI: 3.06-13.28). VL data at 24 months postpartum were available for 89% (366/411) of participants of whom 24% had elevated VL≥1000 copies/ml. Unintended pregnancy was associated with elevated VL in unadjusted analyses [risk ratio (RR): 1.54; CI: 1.03-2.28; p=0.032]. After adjustment for maternal factors and trial allocation, the association persisted despite not reaching statistical significance (adjusted risk ratio (aRR): 1.36; CI: 0.88-2.08; p=0.158). Conclusion: Among postpartum WLWHIV in South Africa, unintended pregnancy is prevalent and could be a risk factor for elevated VL. Reproductive health counselling and support during routine care visits may reduce unintended pregnancies and its effects.

HIV and Tuberculosis (TB) co-infection place an immense burden on health care systems as they act in synergy to worsen disease prognoses. TB is the most common cause of death in people living with HIV (PLWH) and in turn, HIV is the most significant risk factor for progressing from latent to active TB disease. While HIV and TB are endemic in sub-Saharan Africa, they also disproportionately affect marginalized populations in Canada. Unfortunately, the only licensed TB vaccine, BCG, does not protect from adult pulmonary TB and is not recommended for PLWH. Thus, the development of novel TB vaccines, which are safe and effective in PLWH, remains an urgent global necessity. We have found that humanized mice (hu-mice) are ideal models to research this as they can be successfully infected with HIV, TB and HIV/TB and recapitulate human disease pathology. A next-generation respiratory mucosal (RM) trivalent chimpanzee adenoviral-vectored vaccine (Tri:ChAd68) was developed and tested in our naïve and HIV-infected hu-mice. When immunizing naïve hu-mice, a trend of increased M.tb-specific CD4+ T cells producing IFNγ and TNFα in the lungs and spleen was observed. After subsequent M.tb infection, the vaccinated naïve hu-mice also exhibited significantly reduced lung mycobacterial burden, tissue dissemination and lung pathology. We then investigated the vaccine immunogenicity and ability to protect from TB in the context of HIV. Our immunized HIV-infected hu-mice were also able to produce M.tb-specific T cells and when challenged with M.tb, we observed a decreased trend in mycobacterial load in the lungs, indicating that the vaccine may be able to offer protection against TB when a prior HIV infection is present. These findings demonstrate the protective potential of the RM Tri:ChAd68 vaccine against TB disease for PLWH. In the future, we will test this vaccine in antiretroviral treated HIV-infected hu-mice to increase clinical significance. / Thesis / Master of Science in Medical Sciences (MSMS) / HIV and TB are major diseases that can occur together, severely worsening patients’ health and challenging global healthcare systems. The current TB vaccine, BCG, isn’t ideal for people living with HIV (PLWH), causing this vulnerable population to be at greater risk of getting TB infection. Therefore, developing a new TB vaccine that is safe and effective in PLWH is an urgent global issue. We used humanized mice that develop human immune cells to test a novel TB vaccine delivered to the lungs (Tri:ChAd68) to see if it could protect against TB and overcome immune challenges from HIV. We saw increased immune responses and lower TB infection in our vaccinated humanized mice and the vaccine appeared to also be beneficial in the mice that had prior HIV infection. This suggests the Tri:ChAd68 vaccine may be able to offer protection against TB in PLWH; however, more studies are needed to conclude this.

No description available.

This study sought to explore and describe the perceptions and beliefs of physicians about adherence to antiretroviral treatment by patients in the South-East district of Botswana. The Health Belief Model (Naidoo & Willis 2003:222) was adapted to suit and be used in the study. A descriptive, exploratory qualitative design was used. Unstructured interviews and unstructured observation data collection methods were applied. Informed consent was obtained prior to data collection. For triangulation purposes, observations were done following interviews, and data analysis was done by two different people. The findings of the study revealed that the perceptions and beliefs of treating physicians contributed towards adherence. Physicians perceived adherence as an important aspect in the success of antiretroviral treatment. Giving patients correct information, personal motivation, patients' understanding of treatment, traditional and religious beliefs were among other factors perceived by physicians to be impacting on adherence. / Health Studies / M.A. (Public Health)

A qualitative study following a phenomenological approach was undertaken to explore voluntary counselling and testing nurses' perception of educating HIV+ people about ARVs. Non-probability convenience sampling was used and in-depth semi-structured face-to-face interviews were conducted to collect data from 12 participants. The most important results were: &#61623; The need for extensive education on ARVs since it is a new technology used to curb the infection therefore clients need the information in order to use them effectively. &#61623; Stumbling blocks encountered when educating HIV+ people about the drugs. The problems are mainly due to the nurses lack of current knowledge about the drugs; patients' low economic status; severe side effects; difficulties in behaviour change; poor quality of life on ARVs and medical terminology. &#61623; Inability of clients to comply to the regimen because of severe side effects, complex regimen, lack of support from family and friends, lack of motivation, depression, cultural beliefs, lack of knowledge on how to use them and financial constraints. &#61623; Challenges for continuous education because of current nursing shortage, negative attitudes of some nurses, demotivation and inadequate funding for such activity. Recommendations include provision of continuing education and the incorporation of ARV therapy knowledge in the basic nursing curriculum in nursing education. / Health Studies / MA (HEALTH STUDIES)

The aim of the study was to determine the factors that influence adherence to ART among adolescents who contracted HIV through vertical transmission. Qualitative research using descriptive phenomenology was conducted at Botswana-Baylor Children’s Clinical Centre of Excellence. Data was collected using in-depth individual semi-structured interviews. Eight (8) adolescents between 14 and 19 years who had been on ART for minimum of 4 years were interviewed. Thematic analysis of data was done and five (5) themes emerged from the participants' description of the experience of taking ART over a long period of time. The themes that emerged indicated the factors that influence adherence to ART, and they included knowledge and positive beliefs about ART, need for support, ART difficult treatment regimen, having a regular doctor and psychosocial emotional needs. The findings suggested that the adolescents who contracted HIV through vertical transmission require support while continuing on a simplified long-term ART regimen after an assessment of their psychological well beings and periodic checks. / Health Studies / M.A. (Public Health)

Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) is a global problem. Introduction of antiretroviral therapy (ART) came as a relief to people living with HIV and AIDS as it improved their quality of life. However, maintaining high adherence levels to antiretroviral treatment is still a challenge in some settings yet strict adherence to treatment instructions is critical for successful suppression of HIV. A qualitative, descriptive phenomenological research was conducted to explore factors that influence adherence to antiretroviral therapy at Beatrice Road Infectious Disease Hospital (BRIDH). Purposive homogenous sampling was done. Data was collected from twenty patients through in-depth interviews. Study findings identified five main themes that facilitate adherence and these entail knowledge on HIV and AIDS and ART, motivation to live, adherence support networks, good service delivery and factors related to medication / Health Studies / M.A. (Public Health)